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Biomedical subjects

S M Williams

Publications and source records attributed to S M Williams.

At least 127 records · Page 7Linked to original sources

Effect of dietary sodium on airways responsiveness and its importance in the epidemiology of asthma: an evaluation in three areas of northern England.

BACKGROUND: Although several investigations have shown a relationship between asthma (or its surrogate, airways responsiveness) and dietary or urinary sodium, others have not, and the matter remains controversial. This "salt effect" has been investigated during two recent epidemiological surveys of men in northern England. The first assessed the possible effect on airways responsiveness of occupational exposure to welding fumes, and the second characterised airways responsiveness in two geographically distinct residential areas. Thus, three separate study areas/populations were involved. METHODS: Investigation 1 involved 1059 shipyard workers aged 16-27 years who were exposed variously to welding fumes, and Investigation 2 involved 587 men aged 20-44 years who lived in rural West Cumbria or in urban Newcastle upon Tyne. In Investigation 1, a 24 hour urine specimen was requested from each subject with quantifiable airways responsiveness (PD20 < or = 6400 micrograms methacholine) and from an equal number of subjects without measurable airways responsiveness from the same occupational subgroup. In Investigation 2, every subject was asked to provide a 24 hour urine specimen. RESULTS: Of the men undergoing methacholine tests, satisfactory 24 hour urine specimens were obtained from 234 (22.1%) in Investigation 1 and 232 (39.5%) in Investigation 2. Analysis using multiple linear regression, multiple linear logistic regression, and multiple regression for censored data produced consistent results within each study population but conflicting results between them, such that there was no hint of a relationship between airways responsiveness and 24 hour urinary sodium excretion in the shipyard workers of Investigation 1 nor in the rural West Cumbrian population of Investigation 2, but an association was found in the urban Newcastle population of Investigation 2. All study populations were sufficiently large to demonstrate anticipated relationships between airways responsiveness and atopy, baseline FEV1, and (Newcastle only) age. CONCLUSIONS: If airways responsiveness is related to dietary sodium the relationship is not likely to be strong.

Adolescent↗

The role of fibrinolysis in the pathogenesis of the haemorrhagic syndrome produced by virulent isolates of African swine fever virus.

The activity of several proteins involved in fibrinolysis and the morphological changes in the blood vessel walls of pigs infected with highly virulent (Malawi'83) and moderately virulent (Dominican Republic '78-DR'78) ASF virus isolates were determined. Pigs infected with the Malawi'83 virus developed an increased fibrinolytic activity due to high plasma levels of tissue-plasminogen activator (t-PA) of 71.3 +/- 22.8 IU/ml (mean +/- SD), which correlated well with an increased activation of interstitial capillary endothelial cells and high levels of 1150 +/- 73.6 nM of fibrin monomer in the circulation. Animals infected with DR'78 virus, in contrast, showed an inhibition of fibrinolysis in the late stages of disease with almost a 5-fold increase of plasminogen activator inhibitor (PAI) activity of 196.0 AU/ml. These results suggest that activation of the fibrinolytic system in pigs infected with the Malawi'83 virus is probably due to increased formation and deposition of fibrin in the circulation, contributing to an increased bleeding tendency and higher mortality. On the contrary, animals infected with DR'78 virus developed an inhibition of fibrinolysis and thus a reduction in bleeding.

Acute Disease↗

Fetal hemoglobin and potassium in isolated transferrin receptor-positive dense sickle reticulocytes.

A subset of sickle cells have an increased density at the reticulocyte stage of development, indicating that they are either abnormally dense upon release from the bone marrow or become dense quickly in the circulation. These cells are of interest because they most likely have severely disrupted cation regulation and a short lifespan. Based on the distribution of fetal hemoglobin (HbF) in the density fractions of sickle red blood cells (RBCs) and in vitro studies of cellular K+ loss, it seems likely that HbF content is an important in vivo determinant of dense cell formation. In this study, we tested the hypothesis that young, dense cells have low HbF content. Sickle RBCs were first separated into light and dense fractions. Reticulocytes were isolated from unfractionated cells and from each density fraction with an immunomagnetic technique directed against transferrin receptors (TfR) and assayed for the percentage of HbF and K+/Hb ratio. TfR+ reticulocytes isolated from unfractionated cells had a much lower HbF content when compared with all the unfractionated RBCs. This is most likely caused by enrichment of F cells because of a longer circulation life span. Heavy TfR+ reticulocytes had a K+/Hb ratio similar to that measured in the entire dense population and contained very low levels of HbF, averaging 2.5% of the level in all RBCs, 11.7% of the level in all TfR+ reticulocytes, and 4.0% of the level in all dense RBCs. These findings suggest that TfR+ dense cells derive predominantly from non-F cells. Furthermore, the amount of HbF in the circulating dense cells suggests that many of these cells do not derive from the TfR+ dense cells.

Anemia, Sickle Cell↗

Clothing and bedding and its relevance to sudden infant death syndrome: further results from the New Zealand Cot Death Study.

As part of a large nationwide case-control study covering a region with 78% of all births in New Zealand during 1987-90, the clothing and bedding of infants dying of sudden infant death syndrome (SIDS) and that of an appropriate control group were recorded. Cases consisted of 81% (n = 393) of all cases of SIDS in the study area and 88.4% (n = 1592) of 1800 control infants randomly selected from the hospital births and who completed a home interview. Use of a wool 'waterproof' underblanket was associated with a significantly reduced risk of SIDS (adjusted OR 0.44; 95% CI: 0.26-0.73) while sheepskin use was not. Firm tucking was identified as contributing to a reduced risk of SIDS even after adjusting for potentially confounding variables (adjusted OR 0.63, 95% CI: 0.46-0.86). Sixty case infants (15.6% of cases) were found dead with the head covered but there were no equivalent data for controls. Having been found previously completely covered by bedding was equally common in cases and controls (28.8% cases and 30.6% of control infants). Other differences of bedding and clothing between cases and controls were small; mattress characteristics were not studied. The exact methods in which babies are cared for are important and this study suggests that infants are at lower risk of SIDS when firmly tucked in and when sleeping on a 'waterproof' wool underblanket.

Bedding and Linens↗

Alveolar bone loss in 5-year-old New Zealand children: its prevalence and relationship to caries prevalence, socio-economic status and ethnic origin.

This study investigated the prevalence of alveolar bone loss (ABL) in 5-year-old New Zealand children. The relationship of bone loss with the prevalence of caries, socio-economic status and ethnic origin was examined. Standardized bite-wing radiographs from 317 children were used to examine the alveolar bone in 1784 sites. Questionable bone loss (QBL) was evident in 8.5% of the children and definite bone loss (DBL) in 2.1%. The children with suitable radiographs had a mean dmft of 1.8 +/- 2.9 and mean dmfs of 2.7 +/- 5.0. When the children were divided into 3 groups having no bone loss (NBL), QBL only or DBL, analysis of variance on the logarithmic transformation of both the dmft and dmfs scores showed significant differences among the groups. Post hoc tests showed that the means for the DBL group were significantly different from those of the other 2 groups for both dmft and dmfs scores. Logistic regression analysis indicated that the odds ratio for having definite alveolar bone loss was slightly increased in children with a dmft of > or = 9.

Alveolar Bone Loss↗

Image analysis of bromodeoxyuridine (BrdU) staining for measurement of S-phase in rat and mouse liver.

We developed a system for quantifying the numbers of bromodeoxyuridine (BrdU)-labeled hepatocyte nuclei in rat and mouse liver with an automated image analysis system. We began by developing a protocol for BrdU staining that would provide consistently intense staining to facilitate identification of both labeled and unlabeled nuclei by image analysis. Preliminary studies detected and characterized hepatocyte nuclei and differentiated them from non-hepatocyte nuclei using area and form factors. The parameters were selected to optimize discrimination between the two populations, selecting 90% of hepatocyte and 5% non-hepatocyte nuclei. Finally, we developed a program for automatic counting of BrdU-labeled hepatocyte and total hepatocyte nuclei. Results obtained from this method correlated well with data collected by a microscopist over a wide range of labeling indices. The automated system reduces interobserver variation and should minimize intraobserver error, as well as reducing the tedium of measuring labeling indices in the liver. Moreover, the techniques described should be applicable to other tissues.

Animals↗

Long-term comparison of three dietary prescriptions in the treatment of NIDDM.

OBJECTIVE: To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes (NIDDM) in free-living individuals and to observe the effects on metabolic control over an 18-month period. RESEARCH DESIGN AND METHODS: Seventy volunteer subjects with NIDDM were randomly assigned to one of three diets, a weight-management diet, a high-carbohydrate/fiber diet, or a modified-lipid diet and followed for 18 months. Nutrient intakes, weight, blood lipids, and glycemic control were measured. RESULTS: In all diet groups, glycated hemoglobin (HbA1) fell significantly before diet intervention began, remaining lower throughout the study and at follow-up 9 months later. Low-density lipoprotein (LDL) cholesterol showed a sustained fall in all groups after diet intervention. Apart from transient changes in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) in the diet groups with the higher carbohydrate intake, no lasting differences were found between the three diet groups. CONCLUSIONS: In the long term, there were few differences in the outcome of the three dietary prescriptions. Even with intensive instruction, participants found it difficult to meet recommended nutrient intakes; however, specific dietary advice did result in an improvement in LDL cholesterol. Adverse changes in HDL cholesterol and TG because of diet intervention were transient. The significant improvement in glycemic control during the recruitment phase may have been the result of participants' previous dietary knowledge and the increased attention that they received during the intervention.

Analysis of Variance↗

DSM-III-R disorders in New Zealand 18-year-olds.

The one-year prevalence and correlates of selected DSM-III-R disorders were determined in a sample of 930 18-year-olds. Using both diagnostic and impairment criteria 340 individuals (36.6%) were considered to have disorder. The most prevalent disorders were major depressive episode (16.7%), alcohol dependence (10.4%) and social phobia (11.1%). There was a high degree of co-morbidity among disorders; 46% of those with disorder had two or more. The prevalence of disorders was greater for females, with the exception of conduct disorder and alcohol or marijuana dependence. A variety of characteristics were associated with disorder, including poor social competence, disadvantage and self-rated health status. A third of those with disorder had their problems recognised by a "significant-other". The results are presented within the context of a perceived need for research in the area of adolescent and early adult mental health in order to minimise the toll of mental disorder in later life.

Activities of Daily Living↗

Medication and perception of dry mouth in a population of institutionalised elderly people.

AIM: (1) To estimate the prevalence of use of different medication categories; (2) to estimate the prevalence of xerostomia (dry mouth); and (3) to estimate the effects of xerostomic medication upon perceived dry mouth among institutionalised elderly people. SUBJECTS: A two-stage stratified random sample of three hundred and fifty-nine people aged 65 to 102 living in rest homes and geriatric hospitals in the Manawatu and Horowhenua districts. METHOD: Subjects were interviewed and dentally examined at their place of residence. Medication was noted from institutional records, and subjects' experiences of xerostomia were explored using the question "how often does your mouth feel dry?" RESULTS: The sample was found to be highly medicated, with a mean 3.6 different drugs per individual, and only 10% not taking any medication. Psychotherapeutics (42.3%), analgesics (32.9%), diuretics (31.2%) and laxatives (23.4%) were the most common drug categories. Of the 284 subjects who were able to answer, only those who were taking anticholinergic medication reported a higher prevalence of xerostomia. CONCLUSIONS: Institution-dwelling elderly people are a highly-medicated group. There is an increased risk of unwanted oral side-effects with certain drugs, and it is recommended that this is borne in mind when prescribing for elderly patients.

Aged↗

Comparative reproductive success of communally breeding burying beetles as assessed by PCR with randomly amplified polymorphic DNA.

To understand the evolution of alternative reproductive strategies such as communal breeding, it is important to recognize the options open to individuals and to evaluate their consequences. The relative reproductive success of individuals taking each option is one of the most important of these consequences. Burying beetles, Nicrophorus, are an excellent model system for the investigation of reproductive cooperation because they can breed in pairs or communally and provide extensive parental care. In this study, we examine the relationship of the duration of care and the reproductive success of each potentially communally breeding adult. Ten experimental broods reared on mouse carcasses were buried by two males and two females. Using PCR with single short primers that randomly amplify polymorphic DNA, we determined the maternity and paternity of 98.2% and 99.5% of the offspring (n = 217), respectively. In 70% of the broods, both females produced larvae, and in 70%, both males inseminated one or both females. The male and female providing longer care, usually the larger of each sex, were the mother and father of most larvae (50-100%).

Animals↗

Consumption coagulopathy associated with shock in acute African swine fever.

We studied the evolution of shock using a comprehensive array of haematological tests in pigs infected with the highly virulent strain Malawi '83 (Lilongwe 20/1). A sudden onset of illness was observed between day 5 and 7 after inoculation with development of flush, episodes of epistaxis and melaena. Prior to these clinical signs, initiation of a consumption coagulopathy was demonstrated with loss of antithrombin III and plasminogen activity. Our findings indicate that during infection with this highly virulent strain the development of a consumption coagulopathy precedes and possibly contributes to shock, which results in haemorrhage and death.

Acute Disease↗

Haemostatic abnormalities in African swine fever a comparison of two virus strains of different virulence (Dominican Republic '78 and Malta '78).

African swine fever (ASF) virus strains cause haemorrhage by producing a variety of defects, which vary in severity from strain to strain. To distinguish the main haemostatic defects leading to haemorrhage, two groups of pigs were infected with moderately virulent (Dominican Republic '78) and less virulent (Malta '78) ASF virus strains. Mortality rate and severity of clinical observations were greater in pigs infected with DR '78 virus compared with pigs infected with Malta '78 virus. The animals became febrile from day 3 to 4 onwards at a time when the viraemia was high (10(7) to 10(8) HAD50/ml). No difference was found during the period observed in their pattern of viraemia or pyrexia. Thrombocytopenia developed in both groups but with different kinetics, suggesting two different mechanisms of sequestration of platelets. When coagulation tests were performed, significant abnormalities were found, including evidence for disseminated intravascular coagulation. These abnormalities were much less pronounced in the group infected with Malta '78. Antithrombin III activity did not change significantly in either group. Decreased plasminogen activity was found in the early phase of disease in DR '78 infected pigs. These results indicate that when haemorrhage does occur in DR '78 infected pigs, it is a consequence of more pronounced degrees of haemostatic impairment probably due to a marked endothelial injury and/or generation of procoagulant activity.

African Swine Fever↗

The distribution and spreading of rare variants in the histone multigene family of Drosophila melanogaster.

We surveyed the distribution of rare variant restriction sites within and among histone gene arrays of Drosophila melanogaster using restriction fragment length polymorphism (RFLP) analysis. Seventy-three naturally occurring arrays were digested with restriction enzymes that had no recognition sites in the published histone sequence. Of the arrays surveyed, 68.5% had at least two nonconsensus restriction sites present as indicated by the presence of a small band or bands on the autoradiographs. These bands were almost always the length of a single repeat in the histone multigene family or a multiple of this length. In arrays with more than one band, intensity of the bands almost always decreased with increasing size. This shows that within these arrays variant restriction sites were predominantly located on adjacent repeats. If these bands are caused by spreading of variant sites, as is most likely, then variants spread along the array as an inverse function of distance. Overall, if a sequence spread it had a 92% probability of ending up in its nearest neighbor. This pattern may result from the noncontiguous nature of the histone family.

Animals↗

Mental health disorders from age 15 to age 18 years.

OBJECTIVE: To determine the strength of association between mental health disorders in adolescence and disorder in early adulthood. METHOD: The study used mental health data from a longitudinal investigation of a New Zealand birth cohort. Of the 943 with prevalence data for DSM-III disorder at age 15, 890 had prevalence data for DSM-III-R disorder when aged 18 years. RESULTS: Two-thirds of those with disorder at age 15 had disorder at age 18. The residual form of attention deficit disorder, simple phobias, and oppositional disorders (with no other accompanying disorders) were associated with the lowest risk of later disorder and conduct disorder with the highest. With the exception of the overall symptom level, a variety of characteristics examined (e.g., social competence and adversity) could not differentiate between those with transient disorder and those with disorder at both ages. Comparisons of those with recurring disorder and those with new disorder at age 18 showed that in addition to characteristics of the disorder, disadvantage was strongly associated with recurrent disorder. CONCLUSIONS: The risk of later disorder for those with disorder in adolescence was high and differed across type of disorder. Findings suggest that to reduce the risk of disorder in early adulthood, clinicians could play a more active role in community interventions with direct social outcomes.

Adolescent↗

Light and electron microscopic characterization of dopamine-immunoreactive axons in human cerebral cortex.

The distribution and synaptic connections of dopamine axons were studied by light and electron microscopy in human cerebral cortex. For this purpose, dopamine immunoreactivity was characterized in apparently normal anteriolateral temporal cortex, which was removed to gain access to the medial temporal lobe during tumor excision or treatment of epilepsy. Nissl sections showed this to be granular neocortex. Dopamine fibers were distributed throughout this cortex, although there were relatively more fibers in layers I-II and in layers V-VIa, compared to layers III-IV and VIb, resulting in a bilaminar pattern of labeling. In all layers, fibers were seen to form numerous varicosities, and to vary in size from thick to very fine. Fibers were relatively straight, sparsely branched and were oriented in various planes within the cortex. However, in layer I, they often ran parallel to the pial surface. In order to analyze the functional interactions of dopamine fibers, individual cortical layers were surveyed for dopamine synapses. These were usually symmetrical (Gray's type II), although 13% of them were asymmetrical. Approximately 60% of dopamine synapses were made with dendritic spines, and 40% with dendritic shafts, and this ratio was similar in all layers. On both spines and shafts, it was common to see dopamine synapses closely apposed to an unlabeled asymmetric input, suggesting a dopamine modulation of excitatory input. Some postsynaptic dendritic shafts had features of pyramidal cells, including formation of spines. Since pyramidal cells are the major type of cortical spiny neuron, they probably represent the main target of dopamine synapses in this cortex. There were also dopamine profiles apposed to membrane densities on unlabeled axon terminals, suggesting another type of synaptic interaction. These findings provide the first documentation of dopamine synapses in the human cortex, and show that they form classical synaptic junctions. The location of these synapses on spines and distal dendrites, and their proximity to asymmetric synapses, suggest a modulatory role on excitatory input to pyramidal cells.

Axons↗

The synaptology of parvalbumin-immunoreactive neurons in the primate prefrontal cortex.

Electron microscopy and immunocytochemistry with a monoclonal antibody against parvalbumin (PV) were combined to analyze the distribution and morphology of PV-immunoreactive (PV-IR) neurons and the synaptology of PV-IR processes in the principal sulcus of the macaque prefrontal cortex. Parvalbumin-IR neurons are present in layers II-VI of the macaque principal sulcus (Walker's area 46) and are concentrated in a band centered around layer IV. PV-IR cells are exclusively non-pyramidal in shape and are morphologically heterogeneous with soma sizes ranging from less than 10 microns to greater than 20 microns. Well-labeled neurons that could be classified on the basis of soma size and dendritic configuration resembled large basket and chandelier cells. A novel finding is that supragranular PV-IR neurons exhibit dendritic patterns with predominantly vertical orientations, whereas infragranular cells exhibit mostly horizontal or oblique dendritic orientations. PV-IR cells within layer IV exhibit a mixture of dendritic arrangements. Vertical rows of PV-IR puncta, 15-30 microns in length, resembling the "cartridges" of chandelier cell axons were most dense in layers II, superficial III, and the granular layer IV but were not observed in the infragranular layers. Cartridges were often present beneath unlabeled, presumed pyramidal cells. PV-IR puncta also formed pericellular nests around pyramidal cell somata and proximal dendrites, suggestive of basket cell innervation. PV-IR axons were occasionally observed in the white matter underlying the principal sulcus. Electron microscopic analysis revealed that PV-IR somata and dendrites are densely innervated by nonimmunoreactive terminals forming asymmetric (Gray type I) synapses as well as by fewer terminals forming symmetric (Gray type II) synapses. The majority of terminals forming symmetric synapses with PV-IR post-synaptic structures were not immunolabeled; however, some of these boutons did contain PV-immunoreactivity. PV-IR boutons exclusively form symmetric synapses and heavily innervate layer II/III pyramidal cells. PV-IR axon cartridges formed numerous axo-axonic synapses with the axon initial segments of pyramidal cells 15-20 microns beneath the axon hillock and also terminated on large axonal spines of the initial segment. Furthermore, we failed to observe a mixture of PV-immunoreactive and non-immunoreactive boutons composing a single axon cartridge. Pyramidal cell somata and proximal dendrites were also heavily innervated by PV-IR boutons forming symmetric synapses, again, consistent with basket cell innervation. In addition, PV-IR axon terminals frequently formed symmetric synapses with dendritic shafts and spines of unidentified neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗